SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy in C. elegans

Zhang, Yuxia; Yan, Libo; Zhou, Zhidong; Yang, Peiguo; Tian, E; Zhang, Kai; Zhao, Yu; Li, Zhipeng; Song, Bing; Han, Jinghua; Liu, Miao; Zhang, Hong

doi:10.1016/j.cell.2008.12.022

Cited by 224 publications

(339 citation statements)

References 20 publications

Supporting

Mentioning

331

Contrasting

Unclassified

Order By: Relevance

“…Lifespan extension in daf-2 mutants has also been reported to require the autophagy pathway, which operates in a DAF-16-independent manner to recycle proteins and organelles (30,31). Interestingly, P granules are normally removed from the somatic blastomeres in embryos through autophagy (32), which likely clears them from the somatic cells of daf-2 mutants.…”

Section: Discussionmentioning

confidence: 99%

Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

Knutson

Rechtsteiner

Strome

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germ-line traits in somatic cells, to try to confer some of the germ lineage's immortality on the somatic body. Notably, a study in Caenorhabditis elegans suggested that expression of germ-line genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2's long lifespan. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knockdown of individual P-granule and other germ-line genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germ-line program to daf-2's long lifespan and also tested whether other mutants known to express germ-line genes in their somatic cells are long-lived. Our key findings are as follows. (i) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. (ii) Whole-genome transcript profiling of animals lacking a germ line revealed that germ-line transcripts are not up-regulated in the soma of daf-2 worms compared with the soma of control worms. (iii) Simultaneous removal of multiple P-granule proteins or the entire germ-line program from daf-2 worms did not reduce their lifespan. (iv) Several mutants that robustly express a broad spectrum of germ-line genes in their somatic cells are not long-lived. Together, our findings argue against the hypothesis that acquisition of a germ-cell program in somatic cells increases lifespan and contributes to daf-2's long lifespan.germ line | aging | C. elegans | daf-2 | P granules G erm and soma are the two most fundamentally different cell types found in multicellular organisms (1). Germ cells are totipotent and constitute the only immortal lineage, capable of generating entire new organisms generation after generation, whereas somatic cells differentiate into specialized cell types and are mortal, senescing and dying each generation. Maintaining the proper identity of these cell types is essential for propagation of species, and molecular barriers at both the transcriptional and translational levels have evolved to ensure the germ-soma distinction (1). Removal of these barriers in germ cells can lead to both expression of somatic factors and sterility (2-4), whereas removal of these barriers in somatic cells is associated with reentry into the cell cycle and cancer (5, 6). Despite these barriers, it is unknown whether some cell types can tolerate partial fate switching and perhaps adopt traits of other cell types to benefit the organism.An attractive possibility is that acquisition of a germ-cell program by the somatic body can capture some of the immortality of the germ lineage and extend lifespan (7,8). Indeed, a study in Caenorhabditis elegans supports that possibility (9). In C. elegans, inhibition of the insulin-like signaling pathway by a mutation in daf-2 doubles lifespan through activation of the FOXO transcription factor DAF-16...

show abstract

Section: Discussionmentioning

confidence: 99%

Reevaluation of whether a soma–to–germ-line transformation extends lifespan in Caenorhabditis elegans

Knutson

Rechtsteiner

Strome

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The first demonstrated that in C. elegans autophagy mutants, P-granule components erroneously formed foci in somatic cells. 80 A selective autophagy mechanism, depending on interaction of P-granule factors with the protein SEPA-1, was identified that helps clear formation of these aberrant foci. 81 Similarly, stress granules can accumulate in yeast and mammalian cell autophagy mutants, and are targeted by autophagy under various growth and stress conditions.…”

Section: Mrnp Granules Assemble Via Common Mechanismsmentioning

confidence: 99%

mRNP granules

2014

View full text Add to dashboard Cite

“…For example, abnormalities in larval development, synapse formation, and eye development are observed in autophagy gene mutant Drosophila. [8][9][10][11][12] In C. elegans, autophagy genes play a role in apoptotic corpse clearance in embryonic development, 13 the L1 larval stage, 14 and the adult gonad, 15 in degrading germline P granules in somatic cells, 16 and in the selective elimination of paternal mitochondria. 17,18 In mice, autophagy genes play an essential role in preimplantation development, survival during the neonatal starvation period, and in the differentiation of several specific cell lineages, including adipocytes, erythrocytes, and lymphocytes (T cells and B-1a cells) (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%